The broad, long range objectives of this Program Project are to acquire and communicate new, fundamental knowledge on the chemistry, molecular structure, organization and physiological function of the cells and extracellular matrix of connective tissues, with particular reference to bone, cartilage, dentin and enamel. Considerable effort will be directed to studies of tissue calcification and to the features which distinguish the skeletal and mineralized tissues from other connective tissues, since these specific characteristics are likely to play a critical role in defining their biological function. Our research projects cover all levels of anatomical hierarchy and molecular organization and the answers to important questions are being sought by integrating data from a wide diversity of scientific disciplines and techniques, including ultrastructural analysis, biochemistry, biophysics, and bioengineering. We feel that such a multifaceted but concentrated research effort on the basic biology and pathology of the skeletal system at the molecular, cellular, tissue, organ and whole-organism levels will engender a more complete understanding of tissue calcification, calcified tissues and diarthrodial joints and provide a more rational basis for the diagnosis, treatment and prevention of the skeletal diseases that now disable a large part of our population.